Quinolinecarboxylic acids. 3. Synthesis and antibacterial evaluation of 2-substituted-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de] [1,4]benzothiazine-6-carboxylic acids related to rufloxacin.

A series of 2-substituted-7-oxo-2,3-dihydro-1H-pyrido [1,2,3-de] [1,4] benzothiazine-6-carboxylic acids has been prepared and evaluated for in vitro antibacterial activity. These derivatives were less active than corresponding desmethylated analogues. Among these derivatives, the most active compound 9-fluoro-2-methyl-10-(4-methyl-1-piperazinyl)-7-oxo- 2,3-dihydro-1H-pyrido [1,2,3-de] [1,4] benzothiazine-6-carboxylic acid (22a) was selected for preliminary pharmacokinetics in rats. The pharmacokinetic data indicated that (22a) was rapidly absorbed and induced lasting plasma and urinary levels. In comparison with rufloxacin, it was excreted in low quantity in urine; a significant amount of desmethylated piperazinyl urinary metabolite was observed